Tautomerization nitrogen-containing compounds

Many nitrogen-containing compounds engage in a proton-transfer equilibrium that is analogous to keto-enol tautomerism ... 

Reviews have appeared that in part cover recent advances in the ring-chain tautomerism of the nitrogen-containing derivatives of 1,3-dicarbonyl compounds (95ZOB705) of the reaction products of alkenals, alkenones, and alkane-1,3-diones with hydrazines and hydroxylamines (950PP519) and of other compounds [95H(41)1805 95H(41 )2057]. 

Ring-chain tautomerism of nitrogen-containing derivatives of /3-dicarbonyl compounds 90MI8. 

Tautomerism involving phenols is most often seen for Schiff bases, Mannich bases, or o-hydroxyazo aromatics, but is also discussed for o-hydroxynitroso compounds. This is relatively seldom for phenols not having a nitrogen-containing substituent. An exception is 30 and other cases mentioned later. 

Dihydro-1,3,5-triazines are of fundamental interest because of their ability to undergo amidinic tautomerism. Furthermore, as these are nitrogen-containing analogues of dihydropyrimidines (methylene at position 5 replaced by N) it would certainly be interesting to compare the effects of nitrogen substitution on the structual stability and tautomeric behavior of these compounds. 

In many of the nitrogen-containing rings, the hydrogen can shift to produce a tautomer, a compound in which the hydrogen and double bonds have changed position (i.e., -N=C-OH—>-NH-C=0) (Fig. 5.26). Tautomers are considered the same compound, and the structure may be represented either way. Generally one tautomeric form is more reactive than the other. For example, in the two tautomeric forms of uric acid, a proton can dissociate from the enol form to produce urate. 

The NMR spectra of imidoyl halides are not too well investigated. We have utilized NMR spectroscopy to elucidate the structure of arylsulfonyl-chloroformamidines ( ), but no data with regard to the chemical shift of alkyl groups attached to the carbon or nitrogen atom of the —C(X)=N— system is available. Of course, differentiation of the imidoyl halide structure in a-hydrogen containing compounds from the corresponding tautomeric enamine structures is easily accomplished by NMR spectroscopy, provided that the system contains olefinic protons. 

Heterocyclic compounds are ubiquitous in biology, medicine, and biochemistry, and the azoles form an important class of nitrogen heterocyclic compounds with five-membered aromatic rings that can contain one to five nitrogen atoms (other heteroatoms can also be present). Many drugs and pharmaceuticals are derived from azole structures. The structures of representative azoles are shown in Figure 6.1. Note that some of these compounds exist in tautomeric equilibrium in solution. 

A multiply bonded nitrogen atom deactivates carbon atoms a or y to it toward electrophilic attack thus initial substitution in 1,2- and 1,3-dihetero compounds should be as shown in structures (110) and (111). Pyrazoles (110 Z = NH), isoxazoles (110 Z = 0), isothiazoles (110 Z = S), imidazoles (111 Z = NH, tautomerism can make the 4- and 5-positions equivalent) and thiazoles (111 Z = S) do indeed undergo electrophilic substitution as expected. Little is known of the electrophilic substitution reactions of oxazoles (111 Z = O) and compounds containing three or more heteroatoms in one ring. Deactivation of the 4-position in 1,3-dihetero compounds (111) is less effective because of considerable double bond fixation (cf. Sections 4.01.3.2.1 and 4.02.3.1.7), and if the 5-position of imidazoles or thiazoles is blocked, substitution can occur in the 4-position (112). 

Heterocyclic amino compounds including, for instance, 2-aminothiazoles or 2-amino-benzothiazoles, which contain a nitrogen in the ring capable of forming tautomeric structures, yielded the corresponding amides, although in general in lower than usual yield 11381... 

For 2-methyl-5-phenyl-s-triazolo[3,4-61-1,3,4-thiadiazole (350) and 4-methyl-s-triazolo[3,4-6]benzothiazole (182, R = Me), dipole moments were found to be 4.96 and 5.98, respectively.435 For compounds containing only nitrogen as a heteroatom, dipole moment measurements have been used to study annular tautomerism (Section IV,A,1) using Eq. (36).356... 

Most hydroxy-substituted azaheteroaromatic compounds exist predominately in the NH/carbonyl tautomeric form, and such compounds have been widely discussed. By contrast, aza derivatives of cyclopentadienone, and of quinones, although they have received considerable attention in the last 30 years, have never previously been reviewed. In the present overview, we have attempted to collect the information on such derivatives, as well as including l-azetin-4-ones, i.e., of those azaheterocycles which contain in the ring at least one carbonyl group and one or two nitrogen atoms in the form of C=N or N=N bonds. Many of these compounds are unstable but their importance as reactive intermediates is established and many of them could be used as synthons in the preparation of pharmacologically active compounds. 

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